Yeah don't worry about the Skype thing, the phone is built to work with several VoIP apps including Express Talk and Skype. I have two of the phones, and they work well, except for not having speaker phone support.
Ok, here is a list of things to check:
1) What version of ET are you using?
2) Did you install any drivers / CD that came with the phone? To my knowledge you should not do this as NCH has the built-in driver to control and access the phone in Express Talk. If you have the other driver running (the thing with the little phone icon in the system tray) it could cause problems and interfere with the software trying to communicate with the phone.
3) Make sure when you plug in the phone or take your computer out of standby, hibernation or similar that you go into Express Talk and click Options, then OK so the program will essentially reset and attempt to find the USB phone again and interface with it. Otherwise there may be unexpected outcomes.